Featured Research

from universities, journals, and other organizations

Scientists make diseased cells synthesize their own drug

Date:
September 2, 2014
Source:
Scripps Research Institute
Summary:
In a new study that could lead to many new medicines, scientists have adapted a chemical approach to turn diseased cells into unique manufacturing sites for molecules that can treat a form of muscular dystrophy.

Illustration of cells (stock image). "We're using a cell as a reaction vessel and a disease-causing defect as a catalyst to synthesize a treatment in a diseased cell," explained Professor Matthew Disney.
Credit: Jezper / Fotolia

In a new study that could ultimately lead to many new medicines, scientists from the Florida campus of The Scripps Research Institute (TSRI) have adapted a chemical approach to turn diseased cells into unique manufacturing sites for molecules that can treat a form of muscular dystrophy.

"We're using a cell as a reaction vessel and a disease-causing defect as a catalyst to synthesize a treatment in a diseased cell," said TSRI Professor Matthew Disney. "Because the treatment is synthesized only in diseased cells, the compounds could provide highly specific therapeutics that only act when a disease is present. This means we can potentially treat a host of conditions in a very selective and precise manner in totally unprecedented ways."

The promising research was published recently in the international chemistry journal Angewandte Chemie.

Targeting RNA Repeats

In general, small, low molecular weight compounds can pass the blood-brain barrier, while larger, higher weight compounds tend to be more potent. In the new study, however, small molecules became powerful inhibitors when they bound to targets in cells expressing an RNA defect, such as those found in myotonic dystrophy.

Myotonic dystrophy type 2, a relatively mild and uncommon form of the progressive muscle weakening disease, is caused by a type of RNA defect known as a "tetranucleotide repeat," in which a series of four nucleotides is repeated more times than normal in an individual's genetic code. In this case, a cytosine-cytosine-uracil-guanine (CCUG) repeat binds to the protein MBNL1, rendering it inactive and resulting in RNA splicing abnormalities that, in turn, results in the disease.

In the study, a pair of small molecule "modules" the scientists developed binds to adjacent parts of the defect in a living cell, bringing these groups close together. Under these conditions, the adjacent parts reach out to one another and, as Disney describes it, permanently hold hands. Once that connection is made, the small molecule binds tightly to the defect, potently reversing disease defects on a molecular level.

"When these compounds assemble in the cell, they are 1,000 times more potent than the small molecule itself and 100 times more potent than our most active lead compound," said Research Associate Suzanne Rzuczek, the first author of the study. "This is the first time this has been validated in live cells."

Click Chemistry Construction

The basic process used by Disney and his colleagues is known as "click chemistry" -- a process invented by Nobel laureate K. Barry Sharpless, a chemist at TSRI, to quickly produce substances by attaching small units or modules together in much the same way this occurs naturally.

"In my opinion, this is one unique and a nearly ideal application of the process Sharpless and his colleagues first developed," Disney said.

Given the predictability of the process and the nearly endless combinations, translating such an approach to cellular systems could be enormously productive, Disney said. RNAs make ideal targets because they are modular, just like the compounds for which they provide a molecular template.

Not only that, he added, but many similar RNAs cause a host of incurable diseases such as ALS (Lou Gehrig's Disease), Huntington's disease and more than 20 others for which there are no known cures, making this approach a potential route to develop lead therapeutics to this large class of debilitating diseases.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Suzanne G. Rzuczek, HaJeung Park, Matthew D. Disney. A Toxic RNA Catalyzes the In Cellulo Synthesis of Its Own Inhibitor. Angewandte Chemie International Edition, 2014; DOI: 10.1002/anie.201406465

Cite This Page:

Scripps Research Institute. "Scientists make diseased cells synthesize their own drug." ScienceDaily. ScienceDaily, 2 September 2014. <www.sciencedaily.com/releases/2014/09/140902143240.htm>.
Scripps Research Institute. (2014, September 2). Scientists make diseased cells synthesize their own drug. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2014/09/140902143240.htm
Scripps Research Institute. "Scientists make diseased cells synthesize their own drug." ScienceDaily. www.sciencedaily.com/releases/2014/09/140902143240.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
More People Diagnosed With TB In 2013, But There's Good News

More People Diagnosed With TB In 2013, But There's Good News

Newsy (Oct. 22, 2014) The World Health Organizations says TB numbers rose in 2013, but it's partly due to better detection and more survivors. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins